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Cases in CP CML
Expert Insights on Real-world Cases of TKI Therapy for Patients With CP-CML

Released: December 26, 2025

Jerald Radich
Jerald Radich, MD
Neil P. Shah
Neil P. Shah, MD, PhD
B. Douglas Smith
B. Douglas Smith, MD
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Key Takeaways
  • For patients newly diagnosed with chronic-phase CML with a high-risk Sokal score, frontline asciminib is among the preferred treatment options with better tolerability.
  • Low-dose dasatinib provides an alternative dosing option that may lessen toxicity without compromising efficacy in patients experiencing intolerance with imatinib.
  • Treatment-free remission success is associated with being female, having low-risk disease, rapid response to therapy, and durable deep molecular responses.

At the 67th American Society of Hematology (ASH) Annual Meeting held in Orlando Florida, expert faculty Jerald Radich, MD; Neil P. Shah, MD, PhD; and B. Douglas Smith, MD, discussed recent advances in the care of patients with chronic-phase chronic myeloid leukemia (CP-CML) at a live satellite symposium, including several real-world cases covering practical issues in management of patients with approved targeted therapies. Highlighted below are 3 cases covered by the faculty and their perspectives on optimal management.

Patient Case #1:
A 52-year-old female with a history of hypertension, chronic obstructive pulmonary disease, and coronary artery disease status post CABG 2 years ago presents with fatigue, night sweats, and increasing abdominal bloating. A physical exam revealed splenomegaly. Her complete blood count shows white blood cell count 212,000/μL, hematocrit 38%, and platelets 515,000/μL. She has a high Sokal score, and bone marrow biopsy is hypercellular with 3% blasts. Cytogenetic analysis reveals t(9;22); PCR shows BCR::ABL1 transcript (p210) at value of 92% IS. She presents to discuss first-line treatment options for her CP-CML.

Neil P. Shah, MD:
This is an interesting case because we know that imatinib has the lowest risk of cardiovascular toxicities, but this is also a patient with a high Sokal score who, although is not elderly, is not necessarily young. Essentially, we need to decide which of those factors is more important and a case could be made for either asciminib or imatinib based on those characteristics.

Due to a different mechanism of action that results in greater selectivity against the ABL1 kinase, asciminib is associated with improved tolerability compared to first- and second-generation BCR-ABL1 TKIs. Moreover, major molecular response (MMR) rates are improved in patients with intermediate and high-risk disease with the second-generation TKIs or asciminib compared with imatinib. The available data also suggests that the second-generation TKIs and asciminib are superior in terms of achieving deeper complete cytogenetic and molecular responses compared with imatinib and therefore facilitating treatment-free remission (TFR) attempts in a larger proportion of patients. Imatinib is associated with the lowest risk of toxicities that are both serious and irreversible. However, it is also associated with the highest risk of bothersome day-to-day toxicities, particularly in patients with comorbidities (ie, hypertension).

In general, for a patient who is older with significant comorbidities, has reduced life expectancy, or has low-risk disease, imatinib is an acceptable option. Whereas, if they are otherwise healthy with a low EUTOS long-term survival (ELTS) score and a strong desire to achieve a deep molecular response (DMR), then a second-generation TKI or asciminib might be appropriate. Moreover, for patients with high-risk features, we often recommend treatment with a second-generation TKI or asciminib as well.

In the ASC4START trial evaluating asciminib vs nilotinib in newly diagnosed CP-CML, asciminib was better tolerated than nilotinib. However, rate of MMR at 48 weeks was nearly identical. Patients in the asciminib arm achieved responses more rapidly. In summary, there are patient- and disease-specific factors that can help us individualize choice of therapy in the frontline setting.

B. Douglas Smtih, MD:
Knowing that overall survival is not different between the frontline options, is there any reason not to start with imatinib?

Neil P. Shah, MD, PhD:
That is a great question. Part of my hesitancy to start with imatinib vs 1 of the second-generation TKIs or asciminib is that day-to-day tolerability is lower with imatinib. Again, if anything you are looking at a higher likelihood of indefinite therapy with imatinib. I would never say it is wrong to start a patient on imatinib, but my personal preference in general would be a second-generation TKI or asciminib.

Patient Case #2:
Your 52-year-old female patient with newly diagnosed CP-CML with a high Sokal score and past medical history significant for hypertension, chronic obstructive pulmonary disease, and coronary artery disease status post CABG 2 years ago decided to start therapy with imatinib 400 mg daily. Her BCR::ABL1 mRNA transcript levels by RT-PCR were <10% IS at 3 months and <0.1% IS at 12 months. During imatinib, she experienced GI side effects of nausea, frequent bowel movements (6-8/daily with need to wear diapers for travel, all-day activities); muscle aches, cramping; and fluid retention in her legs and puffy eyes most mornings. She is asking to consider changing her TKI to lessen these side effects associated with imatinib.

Which TKI would you consider an optimal switch option for this patient experiencing intolerance to her frontline imatinib 400 mg?

B. Douglas Smith, MD:
In this case, I would change the patient to dasatinib. I may even use low-dose dasatinib at 50 mg once daily because the patient is already responding well to frontline TKI imatinib (in an MMR), and I am switching them for tolerability. Most likely, they could continue with a lower dose.

One question that arises is, “Does every TKI need to be dosed at full strength?” In many of our practices, most patients are not on the recommended full dose. We have data from a propensity score analysis, which evaluated a group of patients who preemptively received dasatinib 50 mg as a starting dose and compared them to a group of patients who were started on dasatinib 100 mg, which is the recommended dose for frontline therapy.

The outcomes of failure-free survival (FFS), event-free survival (EFS), and overall survival (OS) were similar between the dasatinib 50 mg and 100 mg groups. In fact, looking at 4-year FFS, it was statistically different and favored the lower dose of dasatinib (P = .041), whereas treatment-free survival, EFS, and OS were similar between treatment arms. When we look at the achievement of milestone molecular endpoints in this study, including complete cytogenetic response, MMR, MR4, MR4.5, again, the groups achieved similar responses (all P >.05) . In fact, looking at the deeper levels of response, the dasatinib 50 mg group appeared very favorable.

This raises another question of, “How do we optimally dose patients?” Is it always the highest prescribed dose? It may not need to be. In terms of the toxicity profile, again, remarkably similar between groups. Elevations in creatinine and pleural effusions were less frequent with the lower dose. In summary, this low-dose dasatinib strategy could lead to an improvement in tolerability profile in patients trying to switch from imatinib due to tolerability issues without compromising the success of the survival and molecular endpoints.

A recent study presented at the 2025 ASH Annual Meeting (Nayan. ASH 2025. Abstr 5560) evaluated low-dose dasatinib 50 mg vs dasatinib 100 mg vs imatinib 400 mg daily in patients with newly diagnosed CP-CML. The study found better early molecular responses at 3 months with dasatinib 50 mg daily vs the other 2 groups. Low-dose dasatinib was also found to be better tolerated with reduced rates of treatment interruption/discontinuation. Low-dose dasatinib was also less costly.

Patient Case #2 Continued:
Let us continue with our patient. She is now 59 years old and as a reminder was diagnosed with CP-CML approximately 7 years ago with a high Sokal score and past medical history significant for hypertension. Due to previous intolerance to imatinib (diarrhea/swelling of extremities) she was successfully switched to asciminb, which she has been receiving for approximately 72 months now. Her last BCR::ABL1 transcript reading was 0.012%. She expresses concern with the ongoing cost of treatment (financial toxicity) and the drain on her funds for retirement. She is interested in pursuing TFR and asks you what the next steps would be to achieve this.

Jerald Radich, MD:
Now there are 3 key questions in the management of every patient with CP-CML: (1) Who responds to therapy? (2) Who relapses after therapy? And (3) Who can discontinue therapy?

Neil P. Shah, MD, PhD:
In terms of planning for TFR, studies have looked at factors that can be more predictive of success. One of them is female gender, which is predictive of a higher DMR rate and better TFR duration. It is not surprising that patients with low-risk disease initially are more likely to be successful. In terms of transcript level, most patients with CML will have an ABL1 exon 2 fusion. But these can either be with 13 or 14 exons, e13a2 or e14a2, respectively, and it does seem that the 14-exon isoform is associated with a greater likelihood of successful TFR. During treatment, the more rapidly patients respond initially to TKI therapy seems to be a predictor for success, as does duration of treatment and duration of time in a DMR.

We offer TFR attempts to people after at least 3 years of treatment and at least 2 years in a DMR, although it does seem that longer time on treatment and longer time in DMR increases the likelihood of successfully achieving TFR.

Jerald Radich, MD:
We want to be able to identify who is going to respond or who is going to stay in TFR vs who is going to relapse, because you would not want to expose them to a relapse if you did not have to.

Another question is, “Among those patients who have been PCR-negative, are there patients who relapse who could be identified with a more sensitive test?”

To answer this question, we are using digital droplet PCR (ddPCR). A real-time quantitative (RQ)-PCR can be done before discontinuing therapy. If ddPCR was also done and found to be undetectable, very few of those patients relapse. If patients are RQ-PCR-negative and ddpCR-positive, it adds a fair amount of value to predict who is going to relapse and who is not. If you want to attempt TFR for a short period of time and then decide to stay on or not, at 3 months you can essentially identify who will remain in TFR or not based on ddPCR.

Your Thoughts
What challenges have you encountered in managing patients with CP-CML? we encourage you to answer the polling question, visit the program page to download the slides from the live event and watch an on-demand webcast from the live event, and join the conversation in the discussion box below.

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